A recent study by researchers at the Centre for Addiction and Mental Health (CAMH) showed that the brain changes with the progression of depression, suggesting that depression needs to be treated differently at every stage of the illness.

The team, led by Dr. Jeffrey Meyer, showed that people with longer periods of untreated depression — defined as lasting more than a decade — had significantly more brain inflammation compared to those who had less than 10 years of untreated depression.

This study is the first in its field to show biological evidence for how the brain changes in persistent depression. Consequently, it reveals that depression is not a static condition but is instead a degenerative brain disease like Parkinson’s or Alzheimer’s.

They examined how the total distribution volume of translocator protein (TSPO), which is a marker of microglial activation, correlated with the duration of untreated major depressive disorder, total illness duration, and antidepressant exposure.

It was important to study microglial activation, because microglia are involved in the brain’s normal inflammatory responses to trauma or injuries. However, too much inflammation has been associated with degenerative illnesses as well as depression.

Participants from the age of 18–75 were recruited for the study. They were from the Toronto area and CAMH, and they either had major depressive episodes or were healthy. This research was supported by the Canadian Institutes of Health Research, the Brain and Behavior Research Foundation, and the Neuroscience Catalyst Fund.

Using the Positron Emission Tomography, the researchers scanned three primary grey matter regions of interest and 12 additional regions to measure the total distribution volume of TSPO. The researchers also investigated the duration of untreated major depressive disorder, and the combination of total duration of disease and duration of antidepressant treatment.

The research found that the TSPO levels were about 30 per cent higher in different brain regions among those with long-lasting untreated depression, compared to those with shorter periods of untreated depression. The group with long-term depression also had higher TSPO levels than those with no depression.

“An implication of our study is that the current approach for antidepressant treatment isn’t addressing the issue that the illness is changing over time,” said Meyer.

Currently, no matter how long a person has had depression, they are treated with the same approach at every level. Meyer advocates that treatment methods should address the illness differently as it progresses.

However, there is still a lack of evidence in how to treat depression in its later phases. “People can certainly respond to treatment after not responding to previous treatments, but the rate is lower so clinical trials often exclude people who have not responded to a few previous treatments,” said Meyer.

“We are testing whether current treatments for other illnesses could be applied in depression to influence inflammation to make it more curative. There are also new treatments being developed by companies for depression for the same intent,” said Meyer.

Meyer noted that one study is not enough to change the treatment, but he is hopeful that their work will have this impact soon.

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